Efficacy and safety of adapalene gel as a reactive treatment for cetuximab-induced skin toxicity in recurrent or metastatic squamous cell carcinoma of the head and neck: A historical cohort comparison study.

INTRODUCTION: Despite the common occurrence of cetuximab (Cmab)-induced skin toxicity, management strategies are not well established. The traditional mainstay method consists of topical steroids, which, if used excessively, may give rise to other concerns. Alternatively, adapalene can activate epidermal growth factor receptor pathways to potentially alleviate these toxicities. METHODS: We prospectively studied 31 patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) who were eligible to use adapalene gel as a reactive treatment for topical steroid-refractory skin toxicity. For comparison, we retrospectively reviewed 99 patients with R/M SCCHN (historical control cohort) whose skin toxicity was mainly treated with topical steroids. We compared the frequency and severity of Cmab-induced skin toxicity, Cmab therapy status (e.g., dose modification), side effects caused by topical steroids and adapalene gel itself, and other medical interventions. RESULTS: Adapalene gel was used by eight patients (25.8%) in the prospective cohort. Patients in the historical control cohort more frequently required escalation of topical steroid potency (34.3% vs. 12.9%, p = 0.022). Although there was no statistically significant difference in the frequency of grade ≥3 facial skin rash and paronychia between the two cohorts, the prospective cohort showed a significantly shorter time to complete recovery from grade 2/3 paronychia (16 vs. 47 days, p = 0.017). Further, while no skin infections were observed in the prospective cohort, 13 patients in the historical control cohort developed skin infections, especially periungual infection (0% vs. 13.1%, p = 0.024). In addition, no patients in the prospective cohort received a dose reduction of Cmab due to skin toxicities, compared to 20 patients in the historical control cohort (0% vs. 20.2%, p = 0.003). No apparent adapalene gel-related side effects were observed. CONCLUSIONS: Adapalene gel may be an effective management option for topical steroid-refractory Cmab-induced skin toxicities and could improve compliance with Cmab therapy.

Targeting EGFR Exon 20 Insertion Mutation in Non-small cell Lung Cancer: Amivantamab and Mobocertinib.

OBJECTIVE: To evaluate clinical data regarding the use of amivantamab and mobocertinib for epidermal growth factor receptor (EGFR) exon 20 insertion mutation non-small cell lung cancer (NSCLC) and assess their potential impact on the care of patients. DATA SOURCES: A comprehensive literature search of PubMed and Clinicaltrials.gov was conducted using the terms amivantamab, Rybrevant, JNJ-61186372, mobocertinib, Exkivity, TAK-788. STUDY SELECTION AND DATA EXTRACTION: Relevant English-language clinical trials were evaluated. DATA SYNTHESIS: Amivantamab and mobocertinib were Food and Drug Administration (FDA) approved based on phases 1 and 2 studies. Amivantamab demonstrated an overall response rate (ORR) of 40% and median progression-free survival (PFS) of 8.3 months. Patients commonly experienced rash (86%), paronychia (45%), and stomatitis (21%). Mobocertinib demonstrated an ORR of 28% and median PFS of 7.3 months in phase 1/2 study. Patients frequently experienced diarrhea (91%), rash (45%), and paronychia (38%). Cardiac monitoring is recommended with mobocertinib due to risk of QTc prolongation and cardiac failure. RELEVANCE TO PATIENT CARE: For NSCLC patients who possess an EGFR exon 20 insertion mutation, amivantamab and mobocertinib are indicated as second-line therapy. Ongoing studies are evaluating these therapies as first-line monotherapy and as part of combination regimens in multiple cancer types. Dosage forms, drug interactions, and patient comorbidities should be considered when deciding which of the 2 agents may be most appropriate. CONCLUSION: Amivantamab and mobocertinib target an uncommon NSCLC mutation that has historically marked a poor prognosis because of innate resistance to previously approved EGFR tyrosine kinase inhibitors. Promising results from early phase trials supported accelerated FDA approval.

Combination of available topical beta-blockers and antibiotic ointment for epidermal growth factor receptor tyrosine kinase inhibitor-induced paronychia and pseudopyogenic granulomas in Taiwan.

BACKGROUND: Painful paronychia and pseudopyogenic granuloma (PG) are common adverse drug reactions (ADRs) associated with the use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) to treat non-small cell lung cancer (NSCLC). Multiple local management approaches have been tested with unsatisfactory results. We have introduced an occlusion therapy technique through which available topical drugs for longer than 2 years. METHODS: Based on the cancer registry and case management system of our hospital, from July 2019 to July 2020, we retrospectively enrolled patients with NSCLC who were treated with EGFR-TKIs and received applications of 0.5% timolol ophthalmic solution (TIMOPTOL XE 0.5%®) combined with a neomycin/tyrothricin ointment (Biomycin®) using the occlusion method to treat paronychia or PG. RESULTS: A total of 22 patients were enrolled, with a mean age of 66.5 years, most of whom were women (72.7%). Periungual lesion-related pain was reported by all patients, and periungual bleeding and PG were reported in 14% (3/22) and 64% (14/22) of patients, respectively. After the occlusion therapy application of timolol ophthalmic solution combined with neomycin/tyrothricin ointment twice daily, the overall response rate was 83.3%, including complete response in 18% (4/22) of cases and partial response in 68% (15/22) of cases. CONCLUSION: We presented an occlusion method using available topical beta-blockers and antibiotic ointment for EGFR-TKI-induced paronychia and PG in Taiwan. The result is favorable. Further randomized control trial is urgent to validate our findings.

A comparison of panitumumab and cetuximab in the treatment of KRAS wild-type metastatic colorectal cancer: a systematic review and meta-analysis.

AIM: Cetuximab and panitumumab are common antibodies against epidermal growth factor receptor (EGFR) that can be used in combination with chemotherapy for the treatment of metastatic colorectal cancer (mCRC). Although these two drugs are considered to be very similar, differences in the efficacy and safety of cetuximab and panitumumab are still unclear. We conducted this meta-analysis to explore the effects and adverse reactions of cetuximab and panitumumab in the treatment of mCRC. METHODS: We searched PubMed, the Cochrane Library, Embase, Web of Science, China national knowledge infrastructure (CNKI) and WanFang databases to identify records related to the efficacy and safety of cetuximab and panitumumab in the treatment of mCRC. The search terms were "cetuximab," "panitumumab," and "colorectal cancer." The deadline of searching was April 2022. Review manager 5.4 software was used to perform the statistical analysis for this meta-analysis. Pooled hazard ratio (HR) with 95% confidence intervals (CI) were calculated to evaluate the overall survival (OS) and progression free survival (PFS) of cetuximab and panitumumab in the treatment of mCRC. RESULTS: There was no significant difference in OS, PFS, and response rate (RR) between cetuximab arm and panitumumab arm (OS: HR = 0.91, 95% CI = 0.81-1.03, p = .14; PFS: HR = 0.92, 95% CI = 0.83-1.02, p = .11; RR: OR = 1.22, 95% CI = 0.96-1.61, p = .14). We also did not observe any statistical difference between both arms in incidence of acneiform rash, severe acneiform rash, diarrhea, and severe diarrhea (acneiform rash: OR = 1.09, 95% CI = 0.84-1.42, p = .51; severe acneiform rash: OR = 1.50, 95% CI = 0.80-2.81, p = .21; diarrhea: OR = 1.08, 95% CI = 0.82-1.42, p = .58; severe diarrhea: OR = 0.90, 95% CI = 0.44-1.84, p = .77). The incidence of paronychia was decreased in the panitumumab arm, but that of hypomagnesemia and severe hypomagnesemia were decreased in the cetuximab arm. (paronychia: OR = 0.74, 95% CI = 0.55-1.00, p = .05; hypomagnesemia: OR = 1.85, 95% CI =1.41-2.41, p < .00001; severe hypomagnesemia: OR = 2.66, 95% CI = 1.52-4.67, p = .0006). CONCLUSION: There was no significant difference in OS, PFS and RR between the cetuximab arm and panitumumab arm in the treatment of mCRC. For adverse reactions, the incidence of paronychia was decreased in the panitumumab arm, and the incidence of hypomagnesemia was deceased in the cetuximab arm.

Acute paronychia in a neonate secondary to clindamycin-resistant Staphylococcus aureus.

Paronychia is a common inflammatory condition of the nail fold that is often associated with infection. Causes can be fungal, viral, or most commonly, bacterial. Neonatal paronychia is a rare presentation with only one previously reported case in the literature of a patient younger than 1 month of age. This is a case of an 8-day-old neonate with acute bacterial paronychia caused by clindamycin-resistant Staphylococcus aureus.

Atypical paronychia: don't forget herpesvirus.

Paronychia is usually caused by bacterial infections. Herpetic whitlow is an acute infection of the fingers or toes caused by herpes simplex viruses and it typically presents with vesicles. We report the case of a 78-year-old woman with gingivostomatitis and atypical paronychia in several fingers without blisters.

Pemphigus vegetans with paronychia-like changes resistant to rituximab therapy.

Pemphigus vegetans (PVeg) is a clinical variant of pemphigus vulgaris (PV) that makes up about 2% of all cases. It is distinguished from PV by the presence of vegetative plaques that are usually found in the oral mucosa or intertriginous areas. PVeg can present as one of two clinical subtypes: Hallopeau type and Neumann type. The Hallopeau type is a milder form of the disease, often sparing the oral mucosa. The Neumann type is a more severe form that often includes oral mucosal involvement. Nail unit disease of PVeg is rare, lending to limited recommendations for management. Herein, we present a case of PVeg with paronychia-like changes following rituximab therapy, along with a brief review of PVeg nail unit disease management. Previously reported treatments include prednisone, azathioprine, dapsone, and cyclosporine. In this patient with nail disease, despite rituximab therapy, intralesional triamcinolone acetonide was effective, thereby avoiding the need for additional immunosuppression.

Recalcitrant trametinib-induced paronychia treated successfully with topical timolol in a pediatric patient.

Paronychia has been described as a side effect in patients undergoing treatment with MEK (mitogen activated protein kinase enzyme) inhibitors. It is usually a recurrent condition that can have a significant impact in the quality of life. Topical beta blocker treatment has been described as an effective therapy in antineoplastic-induced pyogenic granulomas and in antineoplastic-induced paronychia. We describe the first case treated with topical timolol for a trametinib-induced paronychia in a pediatric patient that allowed to continue the third line antineoplastic therapy for his glioma.

Treatment of MEK inhibitor-induced paronychia with doxycycline.

A 12-year-old girl with neurofibromatosis type 1 and a large facial plexiform neurofibroma had been participating in a selumetinib clinical trial for the past 5 years. Despite decreased tumor size, she developed recalcitrant selumetinib-induced paronychia. Various antibiotics, topical medications, and surgeries were only minimally effective. Full-dose doxycycline resolved the paronychia, and sub-antimicrobial dosing has prevented recurrences for several months, permitting her to continue her selumetinib course.

A randomized phase 2 trial of the efficacy and safety of a novel topical povidone-iodine formulation for Cancer therapy-associated Paronychia.

Purpose Cancer therapy-associated paronychia (CAP) is a frequent adverse event associated with cytotoxic and targeted therapies that may impact dosing of anticancer therapies and patient quality of life (QoL). There are currently no evidence-based management strategies or approved treatments for CAP. Materials and Methods This was a prospective, multicenter, randomized, double-blind, vehicle-controlled phase 2 study that evaluated the efficacy and safety of 6 to 8 weeks of 1% or 2% povidone-iodine (PVP-I) topical solution versus vehicle-control in adult patients with CAP. Patients were randomized to one of three treatment arms administered twice daily: 1% PVP-I (Cohort A), 2% PVP-I (Cohort B), or vehicle-control (Cohort C). The primary endpoint was a two-grade reduction (or reduction to grade 0 if involved nails were grade 1) on the six-point Paronychia Severity Grading (PSG) scale. Secondary endpoints included safety and the effect on QoL and microbiota. Results A total of 102 patients with cancer were randomized to the study. In Cohort A, 83 of 205 (40.5%, P = 0.6059) affected nails met the primary endpoint versus Cohort C. In Cohort B, 88 of 167 (52.7%, P = 0.0063) affected nails met the primary endpoint versus 64 of 169 (37.9%) in Cohort C. Nineteen of 29 patients (65.5%) in Cohort B reported moderately or very painful nails at baseline that decreased to 15 patients (51.7%) at visit 2 and five patients (17.2%) at visit 3. Conclusions Treatment with twice-daily topical 2% PVP-I was safe and resulted in improvement in CAP compared with control. Clinicaltrials.gov identifier: NCT03207906. https://clinicaltrials.gov/ct2/show/NCT03207906.

Are topical beta-blockers really effective "in real life" for targeted therapy-induced paronychia.

Paronychia and periungual pyogenic granuloma represent one of the most common and bothersome dermatologic toxicities observed with ErbB inhibitors. There is no standardized treatment, and management remains challenging. Moreover, conservative management with noninvasive treatment should be promoted for fragile patients in a metastatic setting. Over the last few years, the efficacy of topical blocking agents has been considered for managing cutaneous or mucosal pyogenic granulomas. Very recently, the use of topical propranolol or of timolol has been reported in several patients undergoing treatment with EGFR inhibitors and developing pyogenic granulomas of the nail. We performed a retrospective single-center review of patients with targeted therapy-related paronychia/periungual pyogenic granulomas who had been treated with topical timolol, either alone or in combination with other topical treatments. Nearly two thirds of patients showed at least a partial response after 1 month of therapy, and the use of a topical beta-blocker in our population was associated with a favorable safety profile. Finally, topical timolol may represent a promising treatment option for the management of cancer patients suffering from painful periungual lesions. Comparative clinical trials, however, are still needed.

Paronychia-like cutaneous leishmaniasis.

Chronic paronychia is an inflammatory recalcitrant disorder affecting the nail folds. We report one patient with paronychia revealing ungueal leishmaniasis. A 34-year-old man, resident in the north of Morocco, presented with a 6-month history of an inflamed proximal nail fold of the left thumb, resistant to antibiotics and anti-fungal treatments. En bloc excision of the proximal nail fold was done. The histopathological exam showed epithelioid granulomas with giant cells and the presence of leshmania amastigotes, leading to the diagnosis of ungueal leishmaniasis. Clinical aspects of cutaneous leishmaniasis can be very misleading. The paronychial form is rarely described. In endemic areas it is necessary for the physician to be aware of atypical skin presentations of leishmaniasis.

Clinical and cytologic features of antibiotic-resistant acute paronychia.

BACKGROUND: Acute paronychia usually is treated as a bacterial infection, but antibiotic-resistant acute paronychia may be caused by other infectious and noninfectious problems. OBJECTIVE: We sought to describe the clinical, etiologic, cytologic, and therapeutic features of antibiotic-resistant acute paronychia. METHODS: A retrospective review of medical records and cytology was performed in 58 patients (age, 1 month-91 years; 36 children and adolescents [62%] and 22 adults [38%]) who had antibiotic-resistant acute paronychias. RESULTS: Causes of paronychia included bacteria (25 patients [43%]), viruses (21 patients [36%]), fungi (5 patients [9%]), drugs (3 patients [5%]), pemphigus vulgaris (3 patients [5%]), and trauma (1 patient [2%]). Diagnostic cytologic findings were noted in 54 patients (93%); no diagnostic cytologic findings were present with drug-induced (3 patients) or traumatic (1 patient) paronychia. The most common predisposing factors were the habits of finger- or thumb-sucking (14 patients [24%]) and nail-biting (11 patients [19%]). Complications included id reaction with erythema multiforme in 3 patients (5%). LIMITATIONS: Limitations include retrospective study design from 1 treatment center. CONCLUSION: Antibiotic-resistant acute paronychia may be infectious or noninfectious. Cytologic examination with Tzanck smear may be useful diagnostically and may prevent unnecessary use of antibiotics and surgical drainage.

[Exudative onycholysis and acute bacterial paronychia related to BIBF-1120 and paclitaxel: response to topical therapy]. / Onicólisis exudativa y paroniquia bacteriana aguda en relación con BIBF-1120 y paclitaxel: respuesta a la terapia tópica.

A case of a 50 years-old breast cancer patient treated with weekly paclitaxel and BIBF 1120 is reported herein. At the end of the twelfth cycle of chemotherapy, the patient developed distal onycholysis with intense hyponychium serous exudates, pain and malodor in all her fingernails. It was treated with topical fusidic acid and 1% methylprednisolone aceponate two times daily, with an excellent clinical response from the first three days of treatment. Bacterial paronychia with nail plate loss of the fifth left fingernail was observed a week after the topical therapy was started, with positive cultures for Methicillin susceptible Staphylococcus aureus. There are few reported cases of exudative onycholysis associated with chemotherapy. However, these are especially related to paclitaxel. No recurrences of nail disturbances were observed weeks after the end of chemotherapy. Topical corticosteroids and fusidic acid could be considered as a therapeutic option when exudative onycholysis related to paclitaxel is established

Erlotinib-related skin toxicities: treatment strategies in patients with metastatic non-small cell lung cancer.

Skin toxicities are the most common side effects associated with the epidermal growth factor receptor inhibitor erlotinib, occurring in most patients receiving the drug. Clinical trials evaluating erlotinib for the treatment of non-small cell lung cancer have reported a range of skin disorders, the most common being acneiform rash, xeroderma (dry skin), pruritus, and paronychia. Although in the majority of cases these effects are mild and transient, they can have a considerable impact on a patient's quality of life and, if particularly severe and persistent, may necessitate treatment interruption or cessation and compromise treatment outcome. This coupled with recent evidence to suggest a positive correlation between the incidence and severity of rash and clinical outcome among erlotinib-treated patients with advanced or metastatic non-small cell lung cancer highlights the importance of adequately managing epidermal growth factor receptor inhibitor--related skin disorders. Clear treatment strategies are therefore necessary to ensure the prevention and optimal management of erlotinib-related skin toxicities thereby enabling patients to continue erlotinib treatment. In this review we present a practical approach for the treatment of erlotinib-related cutaneous side effects in Japanese patients with advanced non-small cell lung cancer providing details of specific treatment interventions, according to symptom severity, for each of the common skin disorders. In addition, the importance of preventive skin care measures--namely maintaining cleanliness, moisturization, and protection from external stimuli--in preventing the development of serious skin disorders is discussed and guidelines for the practice of proper skin care are presented.

Histopathological analysis of chronic paronychia.

BACKGROUND: Chronic paronychia is an inflammatory process of the nail folds lasting more than 6 weeks. Clinically, there is hypertrophy and retraction of the folds and absence of the cuticle. Treatment involves clinical measures and, when there is no response or the hypertrophy of the folds is very pronounced, surgical treatment is indicated. Post-surgical histopathology is little studied in the literature. In this sense, we believe that the histopathological study is important not only for the individualized understanding of the patient's chronic disease, avoiding relapses, but also for the understanding of its pathophysiology and treatment possibilities. OBJECTIVE: To describe the histopathological changes found in biopsies of the proximal nail fold of patients with chronic paronychia undergoing surgical treatment. MATERIALS AND METHODS: A histopathological study of 16 nail folds from 6 patients after surgery was performed at 2 study centers. RESULTS: The most prevalent epidermal findings were orthokeratosis, hypergranulosis, acanthosis and spongiosis and the dermal findings were fibrosis and mononuclear inflammatory infiltrate. CONCLUSION: The histopathological study allowed us to conclude that chronic paronychia is primarily an inflammatory process, but it is not possible to conclude whether microorganisms such as Candida and bacterial cocci are part of the etiology or just secondary and opportunistic agents.